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Disulfide Bond Shuffling Induces Molecular Crosstalk: Delayed Insulin Aggregation and Enhanced Neurotoxicity

ABSTRACT: Our study explores the novel concept of disulfide bond shuffling-provoked oligomer crosstalk in insulin. We demonstrate that this dynamic process not only modulates the aggregation kinetics of insulin but also significantly influences its cytotoxic potential. Through a combination of biophysical techniques and cellular assays, we elucidate the molecular mechanisms underlying this phenomenon. Our findings reveal that disulfide bond shuffling in insulin oligomers can lead to the formation of novel, metastable species. These species, in turn, engage in crosstalk with other oligomers, thereby delaying the overall aggregation process. Intriguingly, our data also suggest that these metastable oligomers exhibit enhanced cytotoxicity compared to their fully aggregated counterparts. This observation underscores the potential biological implications of disulfide bond shuffling in insulin and opens up new avenues for investigating the role of protein misfolding and aggregation in disease pathogenesis.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Gongyu Li

LAB HEAD: Gongyu Li

PROVIDER: PXD053868 | Pride | 2025-07-23

REPOSITORIES: Pride

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			Action	DRS
	20231230_1_Control_.A-Za-z0-9.raw	Raw
	20231230_2_Control_.A-Za-z0-9.raw	Raw
	20231230_3_Control_.A-Za-z0-9.raw	Raw
	20231230_4_L_DBS_.A-Za-z0-9.raw	Raw
	20231230_5_L_DBS_.A-Za-z0-9.raw	Raw

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